Long-term enalapril and verapamil in rats with reduced renal mass

Abstract

The effect of long-term treatment with either enalapril or high dose verapamil on survival, proteinuria, blood pressure and renal morphology was studied in female Wistar rats with markedly reduced renal mass. Four weeks were allowed for remnant kidney hypertrophy before determining the response to renal ablation of individual animals regarding proteinuria and hypertension. At this time, five groups of 18 rats were formed with equal levels of proteinuria and hypertension. Groups E1 and E2 were treated with enalapril, groups V1 and V2 with verapamil, and one group served as control. The daily food allowance was 14 g/rat of a standard rat diet, containing 30% protein and 100 mmol NaCl/kg food in groups E1 and V1. NaCl content was reduced to 20 mmol/kg food in groups E2, V2 and control. The drugs were added to the drinking water, enalapril at a dose of 0.1 g/liter, verapamil at 0.5 to 0.7 g/liter. Drug intake thus amounted to 10 to 25 mg/kg for enalapril and 50 to 140 mg/kg for verapamil. Treatment was continued for 15 weeks. Three of the 18 control rats did not survive up to 15 weeks. Mortality was lower in the enalapril treated groups with a single nonsurvivor in group E1. In contrast, mortality was higher in the verapamil treated animals with seven nonsurvivors in group V1 and eight in group V2. Blood pressure control was excellent in both enalapril treated groups. and proteinuria decreased in most animals of group E1 and all of group 22. Glomerulosclerosis did not develop in the majority of the enalapril treated animals. Despite the high dose, verapamil barely lowered blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Control of Hypertension by Yerapamil Enhances Renal Damage in a Rat Remnant Kidney Model

“…The effect of calcium channel blockers on the progression of renal failure is controversial. In contrast with earlier studies, we recently reported that moderately large doses of verapamil significantly accelerated chronic renal failure in the rat remnant kidney model [1]. Studies reporting beneficial effects of verapamil were characterised by a much lower dose of verapamil and by the start of treatment immediately after renal ablation, which potentially interfered with the initial phase of remnant kidney hypertrophy.…”

“…However, in the most extensively studied model of chronic renal failure, the remnantkidney rat, the response to different antihypertensive regimens is not uniform. Control of hypertension by ACE inhibitors has proven to be superior to triple-drug therapy with hydralazine, reserpine, and hydrochlorothiazide regarding prevention or delay in progressive glomerulosclerosis [12], and the highly protective effect of ACE inhibitors was invariably associated with greatly reduced proteinuria [1,12,13].…”

“…Antihypertensive therapy has been shown to retard progressive chronic renal failure in various rat models of experimental renal disease [1][2][3][4][5][6] and also in humans with diabetic nephropathy [7,8] as well as other primary renal diseases [9][10][11]. However, in the most extensively studied model of chronic renal failure, the remnantkidney rat, the response to different antihypertensive regimens is not uniform.…”

Protective Effect of Benidipine against the Development of Glomerular Sclerosis in Experimental Nephrotic Syndrome

“…Histological analysis of tuburointerstitial lesions 94 days after induction of the nephrotic syndrome in vehicle and benidipine (1 or 3 mg/kg, p.o. )-treated rats DISCUSSION Ca-channel blockers, including benidipine, have ameliorating effects on renal function in various animal models of renal failure (2)(3)(4)17). Therefore, Ca-chan nel blockers can be expected to be drugs for protecting against the renal injury.…”

“…In various nephrosis models, hypertension, elevation of glomerular capillary pressure and renal hypertrophy are suggested as important risk factors which accelerate the development of renal disease (1)(2)(3)(4). Some authors reported that antihypertensive agents such as Ca-channel blockers and angiotensin converting-enzyme (ACE) inhibitors normalized the glomerular capillary hydraulic pressure and attenuated the progression of renal disease in a variety of ex perimental renal diseases (2)(3)(4). Thus, some antihyper tensive drugs are now clinically used for renal diseases (5)(6)(7).…”